Summary: Intercellular interactions are critical for a coordinated function of different cell types involved in the immune response. Here we review the cellular and molecular events occurring during cell–cell immune contacts. Cognate naïve CD4+ T lymphocyte-dendritic cell (DC) and primed T cell–antigen-presenting B lymphocyte interactions are discussed. The engagement of cytotoxic T lymphocytes (CTL) or natural killer cells (NK) with their targets is analyzed and compared to the process of T cell–antigen-presenting cell (APC) conjugate formation. The immunological synapse, a complex cluster of molecules organized at the contact area of cell conjugates, exhibits common features but shows some differences depending on cell types involved. Cellular interactions occur in sequential stages that involve dramatic changes in cell polarity and dynamic redistribution of cell membrane receptors. The role of membrane microdomains, adaptor molecules and the cytoskeleton in the regulation of the molecular reorganization at cell–cell contacts is also discussed.